Submissions for variant NM_032608.7(MYO18B):c.6825G>A (p.Trp2275Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Division of Medical Genetics, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi	RCV003236235	SCV003932678	likely pathogenic	Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome		criteria provided, single submitter	research
Neuberg Centre For Genomic Medicine, NCGM	RCV003236235	SCV004175801	likely pathogenic	Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome	2023-02-14	criteria provided, single submitter	clinical testing	The stop gained variant c.6825G>A (p.Trp2275Ter) in the MYO18B gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has 0.0009% allele frequency in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. It has been submitted to ClinVar as Likely Pathogenic. This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease-causing (Malfatti et al., 2015). For these reasons, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003779856	SCV004660190	pathogenic	not provided	2023-07-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2506003). This variant has not been reported in the literature in individuals affected with MYO18B-related conditions. This variant is present in population databases (rs763487608, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Trp2275*) in the MYO18B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO18B are known to be pathogenic (PMID: 25748484, 32184166, 32637634).